Regional differences in the effects of various doses of cerulein upon the small-intestinal migrating motor complex in fasted and non-fasted sheep

There are no precise data concerning the effect of cerulein on the small-intestinal migrating motor complex (MMC) in sheep. Thus, the effort was directed towards the elucidation of the role of cerulein, a cholecystokinin (CCK) amphibian analogue, in the regulation of MMC cycle in conscious fasted and non-fasted sheep in various regions of the small intestine. In six sheep, equipped with bipolar electrodes in the entire small intestine and with one duodenal strain gauge force transducer in four of these animals, the continuous myoelectric and motor activity recordings were performed. During control period, two normal consecutive MMC cycles were recorded in fasted and non-fasted animals and then cerulein was slowly injected at the dose 1 (during 30 s), 10 (during 30 s or 60 s) or 100 ng/kg (during 30 s, 60 s or 120 s) or infused at the dose 0.5 or 1.5 ng/kg/min during 60 min. After cerulein administration at least two consecutive MMC cycles were also recorded. It was found that cerulein in moderate and higher doses injected in both fasted and non-fasted animals, especially during phase 2a or 2b MMC, inhibited phase 3 in the duodenum in at least one-third of the experiments and significantly increased the MMC cycle duration. The application of 100 ng/kg of cerulein during 120 s in the course of phase 2b MMC prolonged cycle duration from 70 +/- 21 to 113 +/- 19 min (p < 0.05) or from 51 +/- 18 to 113 +/- 19 min (p < 0.01) in fasted and non-fasted sheep respectively. The first phase 3 MMC arriving after cerulein administration at the highest dose was usually abnormal in approximately 60% of the experiments. The second phase 3 observed following the hormone injection was abnormal much less frequently and to the lesser extent. Furthermore, both cerulein doses significantly shortened the duration of phase 3 MMC either in fasted (from approximately 5.5-6.5 cpm to 4-5 cpm) or in non-fasted sheep (from approximately 4.5-5.5 to 3-4.5 cpm). The effects of cerulein exhibited the dose-response character. They were more pronounced when cerulein was injected during phase 2b or 2a MMC when compared with phase 1 MMC. The effects of cerulein on the ileal MMC were less evident, although the inhibition of the ileal phase 3 in response to both higher injected doses was observed occasionally. Infusions of cerulein in non-fasted sheep exerted similar effects as cerulein injections. It was stated that cerulein exerts marked regulatory effect upon the small-intestinal MMC in sheep. Although it remains uncertain whether the efficient doses of cerulein used in the present study correspond to physiological or pharmacological doses of CCK it seems likely that most of these doses were physiological. Thus, it is concluded that cerulein participates in the control of MMC cycles in the digestive and interdigestive states in sheep. It is possible that CCK is a physiological regulator of the ovine small-intestinal MMC.